This invention provides an improved pharmaceutically elegant tablet formulation of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine, hereinafter referred to as olanzapine, and processes for the preparation thereof.
Olanzapine has shown great promise in the treatment of psychotic patients and is currently being evaluated for that purpose. Certain tablet formulations of olanzapine are known, as described in U.S. Pat. No. 5,229,382. However, improved oral formulations were desired in light of the moisture sensitive, metastable nature of olanzapine, the tendency of olanzapine to undesirably discolor in the known tablet formulation, and due to the surprisingly potent nature of olanzapine.
The presently claimed invention provides a pharmaceutically elegant solid oral formulation comprising olanzapine as an active ingredient intimately mixed with a bulking agent, binder, disintegrant, a dry binder to provide friability, and a lubricant;
wherein such solid oral formulation is coated with polymer selected from the group consisting of hydroxypropyl methyl cellulose, hydroxyethyl cellulose,
methylhydroxyethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, polyvinyl pyrrolidone, dimethylaminoethyl methacrylatemethylacrylate acid ester copolymer, ethylacrylate-methylmethacrylate copolymer, methylcellulose, and ethylcellulose.
It is particularly preferred that the polymer coat does not contain polyethylene glycol.
Further, the invention provides a method for preparing pharmaceutically elegant, stable solid oral olanzapine formulations having a polymer coat selected from the group consisting of hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methylhydroxyethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, polyvinyl pyrrolidone, dimethylaminoethyl methacrylatemethylacrylate acid ester copolymer, ethylacrylate-methylmethacrylate copolymer, methylcellulose, and ethylcellulose, comprised of using a high shear aqueous wet granulation with fluid bed drying process.